Redox-active iron mediates amyloid-beta toxicity

While amyloid-beta toxicity is mediated by oxidative stress and can be attenuated by antioxidants, the actual biochemical mechanism underlying neurotoxicity remains to be established. However, since aggregated amyloid-beta can interact with transition metals, such as iron, both in vitro and in vivo, we suspected that bound iron might be the mediator of toxicity such that holo- and apo-amyloid would have differential effects on cellular viability. Here we demonstrate that when amyloid-beta is pretreated with the iron chelator deferoxamine, neuronal toxicity is significantly attenuated while conversely, incubation of holo-amyloid-beta with excess free iron restores toxicity to original levels. These data, taken together with the known sequelae of amyloid-beta, suggest that the toxicity of amyloid-beta is mediated, at least in part, via redox-active iron that precipitates lipid peroxidation and cellular oxidative stress.     

MiR-204 regulates cardiomyocyte autophagy induced by ischemia-reperfusion through LC3-II

Background  

Autophagy plays a significant role in myocardial ischemia-reperfusion (IR) injury. So it is important to inhibit autophagy to protect cardiomyocytes besides anti-apoptosis. MiRNA has been demonstrated to protect cardiomyocytes against apoptosis during IR, while whether it has anti-autophagy effect has not been known. The aim of this study was to investigate whether miR-204 regulated autophagy by regulating LC3-II protein, which is the marker of autophagosome during myocardial IR injury.     

不同光强下红松幼树光合作用和营养物质含量的季节模式

一、前言原始红松林下幼树生长缓慢,死亡率高,若干文献通过与桦木林光照和水热条件的对比观察,认为光是影响生长的主要原因。但同时也发现,在植物一切代谢活动最旺盛的生长季(6—9月),上述二种林下的光强(lx)     

瘤胃降解粗纤维产甲烷的厌氧真菌与甲烷菌共培养物的分离鉴定

【目的】本试验从瘤胃中分离鉴定降解粗纤维产甲烷的厌氧真菌与甲烷菌共培养物,为深入探究甲烷菌对厌氧真菌代谢途径的影响及相关调节机制奠定基础。【方法】利用厌氧滚管技术从荷斯坦奶牛瘤胃内容物中分离厌氧真菌与甲烷菌共培养物,通过形态学观察和DAPI染色以及甲烷菌16S rRNA基因序列分析方法分别对厌氧真菌及甲烷菌进行鉴定。【结果】从荷斯坦奶牛瘤胃中共分离到28株厌氧真菌与甲烷菌共培养物。共培养物中的厌氧真菌均为单中心菌株,分别属于Piromyces,Neocallimastix和Caeomyces属,所占百分比为53.57%,42.86%及3.57%。甲烷菌16S rRNA基因序列分析结果表明,共培养物中的甲烷菌均为甲烷短杆菌。本研究共获得四种不同的厌氧真菌与甲烷菌组合,分别为Piromyces/类Methanobrevibacter olleyae菌株,Neocallimastix/类Methanobrevibacter olleyae菌株,Neocallimastix/类Methanobrevibacter thaueri菌株及Caecomyces/类Methanobrevibacter olleyae菌株,分别占总数的53.57%,39.29%,3.57%及3.57%。【结论】分离得到的28株厌氧真菌和甲烷菌共培养物中,占优势的为具有丰富丝状假根的厌氧真菌Piromyces和Neocallimastix以及类Methanobrevibacter olleyae属的甲烷短杆菌。本研究为进一步研究瘤胃内厌氧真菌与甲烷菌相互代谢关系奠定基础。     

Testing the responses of four wheat crop models to heat stress at anthesis and grain filling

Higher temperatures caused by future climate change will bring more frequent heat stress events and pose an increasing risk to global wheat production. Crop models have been widely used to simulate future crop productivity but are rarely tested with observed heat stress experimental datasets. Four wheat models (DSSAT‐CERES‐Wheat, DSSAT‐Nwheat, APSIM‐Wheat, and WheatGrow) were evaluated with 4 years of environment‐controlled phytotron experimental datasets with two wheat cultivars under heat stress at anthesis and grain filling stages. Heat stress at anthesis reduced observed grain numbers per unit area and individual grain size, while heat stress during grain filling mainly decreased the size of the individual grains. The observed impact of heat stress on grain filling duration, total aboveground biomass, grain yield, and grain protein concentration (GPC) varied depending on cultivar and accumulated heat stress. For every unit increase of heat degree days (HDD, degree days over 30 °C), grain filling duration was reduced by 0.30–0.60%, total aboveground biomass was reduced by 0.37–0.43%, and grain yield was reduced by 1.0–1.6%, but GPC was increased by 0.50% for cv Yangmai16 and 0.80% for cv Xumai30. The tested crop simulation models could reproduce some of the observed reductions in grain filling duration, final total aboveground biomass, and grain yield, as well as the observed increase in GPC due to heat stress. Most of the crop models tended to reproduce heat stress impacts better during grain filling than at anthesis. Some of the tested models require improvements in the response to heat stress during grain filling, but all models need improvements in simulating heat stress effects on grain set during anthesis. The observed significant genetic variability in the response of wheat to heat stress needs to be considered through cultivar parameters in future simulation studies.     

球毛壳菌(Chaetomium globosum)NK102 纤维素酶基因及其表达条件

[目的]生物质的利用是当前生物技术研究的一个热点.本小组分离到一株高效降解纤维素球毛壳菌(Chaetomium globosum)NK102,本文拟探索研究此菌的纤维素酶表达系统并寻找影响酶基因表达的关键因素.[方法]通过对NK102测序,本文界定了球毛壳菌NK102的主要纤维素酶编码基因,使用数字基因表达谱升级版(RNA-Seq)的方法得到纤维素酶基因的表达差异,然后观察了营养、物理条件下纤维素酶基因表达和酶活性变化的情况.[结果]发现随着培养时间的延长,纤维素酶基因整体上表达量升高.在所选基因中,外切葡聚糖酶、纤维二糖脱氢酶和内切葡聚糖酶基因(cbh1,cdh和egl1)的表达量最高.糖代谢的负调控因子ACE I和CreA的随时间表达量均降低,而Hap2/3/5复合体的表达量反而升高.之后检测了不同碳源培养基对纤维素酶基因表达量和酶活性的影响,发现葡萄糖为强阻遏因子,纤维二糖为其诱导物,而山梨醇没有影响.特别是,我们发现光照也影响纤维素酶基因的表达,黑暗条件明显抑制酶基因的表达.[结论]转录组学的方法可以初步探索纤维素酶表达的规律,酶基因的表达受到营养、物理条件的影响.本研究为揭示球毛壳菌降解纤维素分子机理和阐释生物质糖代谢途径提供了有用参考.     

An alternative-exon database and its statistical analysis

We compiled a comprehensive database of alternative exons from the literature and analyzed them statistically. Most alternative exons are cassette exons and are expressed in more than two tissues. Of all exons whose expression was reported to be specific for a certain tissue, the majority were expressed in the brain. Whereas the length of constitutive exons follows a normal distribution, the distribution of alternative exons is skewed toward smaller ones. Furthermore, alternative-exon splice sites deviate more from the consensus: their 3' splice sites are characterized by a higher purine content in the polypyrimidine stretch, and their 5' splice sites deviate from the consensus sequence mostly at the +4 and +5 positions. Furthermore, for exons expressed in a single tissue, adenosine is more frequently used at the -3 position of the 3' splice site. In addition to the known AC-rich and purine-rich exonic sequence elements, sequence comparison using a Gibbs algorithm identified several motifs in exons surrounded by weak splice sites and in tissue-specific exons. Together, these data indicate a combinatorial effect of weak splice sites, atypical nucleotide usage at certain positions, and functional enhancers as an important contribution to alternative-exon regulation.     

Optimization of novel monobactams with activity against carbapenem-resistant Enterobacteriaceae – Identification of LYS228

Metallo-β-lactamases (MBLs), such as New Delhi metallo-β-lactamase (NDM-1) have spread world-wide and present a serious threat. Expression of MBLs confers resistance in Gram-negative bacteria to all classes of β-lactam antibiotics, with the exception of monobactams, which are intrinsically stable to MBLs. However, existing first generation monobactam drugs like aztreonam have limited clinical utility against MBL-expressing strains because they are impacted by serine β-lactamases (SBLs), which are often co-expressed in clinical isolates. Here, we optimized novel monobactams for stability against SBLs, which led to the identification of LYS228 (compound 31). LYS228 is potent in the presence of all classes of β-lactamases and shows potent activity against carbapenem-resistant isolates of Enterobacteriaceae (CRE).